Care,agency and criminality: Making sense of authorised extended distribution in the accounts of key stakeholders

IntroductionOne of the current harm reduction debates in Australia concerns the legalisation of the extended distribution of sterile needles and syringes, a practice that is currently unlawful in most Australian settings.MethodsWe used data from a unique pilot program of authorised extended distribution to document the opinions held by 22 key stakeholders -service staff, drug users and police - about the risks and benefits of authorisation, and to analyse the ways in which drug users were understood within these.ResultsOpinions were strongly in favour of authorising extended distribution, based on the belief that this would reduce the transmission of hepatitis C. However, stakeholders also identified that distributors risked attention from police and some noted that the consequences of this would be borne by distributors themselves and not the services that support them. These opinions rested on specific assumptions about people who inject, some of which reflect negative constructions of drug users as a source of danger to the public or as helpless ‘addicts’ with little control over their risk reduction. But there were other representations that positioned drug users more positively as responsible agents with a strong duty of care to themselves and others whose choices are often limited by inadequate service structures. Staff participants drew on these understandings in careful and strategic ways, arguing for the rationality and expertise of drug users, while also problematizing the individualised approach that any form of authorised extended distribution might take.ConclusionWe argue that localised and incremental changes such as those that took place to support this pilot project, and the extensive support for extended distribution among stakeholders in this study including police, creates meaningful opportunities to think about extended distribution differently, which can in turn support conditions for future discussions about legislative change.     

Alterations in energy consumption and plantar pressure distribution during walking in young adults with patellofemoral pain syndrome

Objective

The aim of this study was to determine the alterations of walking energy expenditure and plantar pressure distribution in young adults with patellofemoral pain syndrome (PFPS).

中医药分期防治新型冠状病毒肺炎的药性功效分析

新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)疫情严峻复杂,探讨中医药防治COVID-19处方的用药规律及特点具有重要意义。该研究收集2020年1月1日至2月18日国家卫生健康委员会,7个省市卫生健康委员会、国家中医管理局发布的和《新型冠状病毒肺炎中医诊疗手册》收录的中医药防治COVID-19诊疗方案以及3位国医大师、4位知名中医药专家所拟的方药,按照纳入、排除标准进行筛选,应用EpiData 3.0软件,建立"防治新型冠状病毒肺炎中医处方库""防治新型冠状病毒肺炎常用中药库",共收集有效中药处方93首,组成药物共计157味。应用SPSS 18.0软件进行数据分析,结果发现:①药性寒、温居多,其中性寒69味,占43.95%;性温57味,占36.31%;性热较少,仅占1.27%;②味苦、辛、甘药物较多,不同时期药味有异,初期以辛味居多,中期、重症期以苦味为主,恢复期多用甘味药;③归经以入肺、胃、心者多,入肺经最多,占24.55%;初、中期多入肺胃,重症期则入心肾;④口服药物多无毒,仅6味药物具有毒性,分别是苦杏仁、绵马贯众、重楼、细辛、半夏、炮附片;⑤以具有解表、化湿、清热、补虚、化痰止咳平喘5类功效的药物居多,初期解表与清热并重,各占18.81%;中期化痰止咳平喘药物使用多,占29.61%;重症期清热使用最多,占33.33%;恢复期补虚使用最多,占36.47%。中药防治COVID-19的药性特点和功效分布与中医对其病因、病位、病机的认识紧密相关,临证辨治尤需注重分期用药及因地制宜。     

Visualization of electrophysiological activity at the carpal tunnel area using magnetoneurography

ObjectiveTo establish a noninvasive method to measure the neuromagnetic fields of the median nerve at the carpal tunnel after electrical digital nerve stimulation and evaluate peripheral nerve function.MethodsUsing a vector-type biomagnetometer system with a superconducting quantum interference device, neuromagnetic fields at the carpal tunnel were recorded after electrical stimulation of the index or middle digital nerve in five healthy volunteers. A novel technique for removing stimulus-induced artifacts was applied, and current distributions were calculated using a spatial filter algorithm and superimposed on X-ray.ResultsA neuromagnetic field propagating from the palm to the carpal tunnel was observed in all participants. Current distributions estimated from the magnetic fields had five components: leading and trailing components parallel to the conduction pathway, outward current preceding the leading component, inward currents between the leading and trailing components, and outward current following the trailing component. The conduction velocity and peak latency of the inward current agreed well with those of sensory nerve action potentials.ConclusionRemoving stimulus-induced artifacts enabled magnetoneurography to noninvasively visualize with high spatial resolution the electrophysiological neural activity from the palm to the carpal tunnel.SignificanceThis is the first report of using magnetoneurography to visualize electrophysiological nerve activity at the palm and carpal tunnel.     

Land- versus water-walking interventions in older adults: Effects on body composition

ObjectivesIncreasing physical activity is a priority worldwide, including for older adults who may have difficulty performing traditional forms of exercise, and for whom retention of muscle mass is an important consideration. Water-based exercise may provide an alternative if benefits are comparable. We compared the impact on body composition of 24-week water- versus land-walking interventions in healthy but inactive older adults.DesignRandomised, controlled trial.Methods72 participants (62.5 ± 6.8 yr) were randomised to a land-walking (LW), water-walking (WW) or control (C) group in a supervised centre-based program. The exercise groups trained 3 times/week at matched intensity (%HRR), increasing from 40–45% to 55–65% heart rate reserve (HRR). Height, weight, body mass index (BMI), waist and hip girths were recorded; dual X-ray absorptiometry (DXA) provided fat and lean tissue masses. Participants were re-assessed 24 weeks after completion of the intervention.ResultsThere were no significant changes in body mass or BMI following either exercise protocol, however central adiposity was reduced in both exercise groups, and the WW group increased lower limb lean mass. These benefits did not persist over the follow-up period.ConclusionsExercise can confer beneficial effects on body composition which are not evident when examining weight or BMI. Both WW and LW improved body composition. Water walking can be recommended as an exercise strategy for this age group due to its beneficial effects on body composition which are similar to, or exceed, those associated with land-walking. For benefits to persist, it appears that exercise needs to be maintained.     

傣族药产地生态适宜性分析与产业发展策略

适宜性产区能够保障傣族药的品质,然而有关植物类傣族药适宜生态因子及适宜产区的研究目前较为匮乏。本研究利用中药材产地适宜性分析地理信息系统(GMPGIS)对植物类傣族药进行全国产地生态适宜性分析,首次提出了植物类傣族药主要分布区域的生态因子范围和主要土壤类型,如年均温8. 6～23. 7℃,年均降水量1 212～1 881 mm,年均日照149. 7～157. 4 W·m-2,主要土壤类型为强淋溶土、冲积土、高活性强酸土等。以179个采样点为基础,通过生态相似性分析得到植物类傣族药在全球范围内的最大生态相似度区域,主要包括中国、巴西、美国、缅甸、老挝等国家。在中国主要集中在云南的西部和南部,包括西双版纳傣族自治州、德宏傣族景颇族自治州普洱市、保山市、临沧市具有较大的适宜栽培区域。除此之外,本文通过分析傣族药人才匮乏、傣族药资源日益减少、文化传承具有局限性、科学研究薄弱等问题,并提出了通过傣族医药高素质人才培养、傣族药资源调研和保护工作、推进傣族药资料古籍的搜集整理、加强傣族药基础研究和应用研究等策略促进傣族医药发展。本研究为指导植物类傣族药生产基地合理布局、引种繁育等提供依据,为高品质傣族药的科学规范化生产奠定基础。     

Comparative pharmacokinetics and tissue distribution of cryptotanshinone,tanshinone IIA,dihydrotanshinone I,and tanshinone I after oral administration of pure tanshinones and liposoluble extract of Salvia miltiorrhiza to rats

Salvia miltiorrhiza is one of the most commonly used traditional Chinese medicines in the treatment of cardiovascular and cerebrovascular diseases. Cryptotanshinone (CTS), tanshinone IIA (Tan IIA), dihydrotanshinone I (diTan I), and tanshinone I (Tan I) are the main active compounds in the liposoluble extract of Salvia miltiorrhiza. The differences in the pharmacokinetic and tissue distribution behaviors of the four tanshinones after oral administration of the liposoluble extract of Salvia miltiorrhiza and pure compounds are not clear. This study aims to compare the pharmacokinetics and tissue distribution of the four tanshinones after oral administration of pure tanshinone monomers and the liposoluble extract of Salvia miltiorrhiza. An ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) analysis method was developed for the determination of the four tanshinones. The results showed that the AUC and C_max of tanshinones in rats receiving the extract of Salvia miltiorrhiza were significantly increased compared with those receiving the pure tanshinones. In the tissue distribution experiments, the AUC of the four tanshinones in the extract was much greater than the AUC of the monomers in the lung, heart, kidney, liver, and brain, and the coexisting constituents particularly promoted the distribution of tanshinones into tissues that the drug cannot sufficiently penetrate. These findings suggested that the coexisting constituents in the liposoluble extract of Salvia miltiorrhiza play an important role in the alteration of plasma concentration and tissue distribution of the four tanshinones. Understanding these differences could be of significance for the development and application of Salvia miltiorrhiza extract and tanshinone components.     

Bayesian leveraging of historical control data for a clinical trial with time-to-event endpoint

The recent 21st Century Cures Act propagates innovations to accelerate the discovery, development, and delivery of 21st century cures. It includes the broader application of Bayesian statistics and the use of evidence from clinical expertise. An example of the latter is the use of trial-external (or historical) data, which promises more efficient or ethical trial designs. We propose a Bayesian meta-analytic approach to leverage historical data for time-to-event endpoints, which are common in oncology and cardiovascular diseases. The approach is based on a robust hierarchical model for piecewise exponential data. It allows for various degrees of between trial-heterogeneity and for leveraging individual as well as aggregate data. An ovarian carcinoma trial and a non-small cell cancer trial illustrate methodological and practical aspects of leveraging historical data for the analysis and design of time-to-event trials.     

Design,synthesis and pharmacological evaluation of 4-(3-chloro-4-(3-cyclopropylthioureido)-2-fluorophenoxy)-7-methoxyquinoline-6-carboxamide (WXFL-152): a novel triple angiokinase inhibitor for cancer therapy

Angiokinases, such as vascular endothelial-, fibroblast- and platelet-derived growth factor receptors (VEGFRs, FGFRs and PDGFRs) play crucial roles in tumor angiogenesis. Anti-angiogenesis therapy using multi-angiokinase inhibitor has achieved great success in recent years. In this study, we presented the design, synthesis, target identification, molecular mechanism, pharmacodynamics (PD) and pharmacokinetics (PK) research of a novel triple-angiokinase inhibitor WXFL-152. WXFL-152, identified from a series of 4-oxyquinoline derivatives based on a structure–activity relationship study, inhibited the proliferation of vascular endothelial cells (ECs) and pericytes by blocking the angiokinase signals VEGF/VEGFR2, FGF/FGFRs and PDGF/PDGFRβ simultaneously in vitro. Significant anticancer effects of WXFL-152 were confirmed in multiple preclinical tumor xenograft models, including a patient-derived tumor xenograft (PDX) model. Pharmacokinetic studies of WXFL-152 demonstrated high favourable bioavailability with single-dose and continuous multi-dose by oral administration in rats and beagles. In conclusion, WXFL-152, which is currently in phase Ib clinical trials, is a novel and effective triple-angiokinase inhibitor with clear PD and PK in tumor therapy.